Background and objectives There is a need for local anesthetics that provide consistent analgesia through 72 hours after surgery. This study evaluates the use of HTX-011 (bupivacaine and meloxicam in Biochronomerpolymer technology), an extended-release, dual-acting local anesthetic, in reducing both postoperative pain over 72 hours and postoperative opioid use when compared with bupivacaine hydrochloride (HCl) and saline placebo. Inclusion of low-dose meloxicam in HTX-011 is designed to reduce local inflammation caused by surgery, potentiating the analgesic effect of bupivacaine. Previously, significant synergy has been observed with bupivacaine and meloxicam with both given locally together.

Methods EPOCH 1 was a randomized, double-blind, placebo-controlled and active-controlled phase III study in subjects undergoing a primary unilateral, distal, first metatarsal bunionectomy in which subjects received either a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl or saline placebo.

Results A total of 412 subjects were dosed. The results for the primary and all four key secondary endpoints were statistically significant in favor of HTX-011. HTX-011 demonstrated superior, sustained pain reduction through 72 hours, significantly reduced opioid consumption and resulted in significantly more opioid-free subjects compared with saline placebo and bupivacaine HCl. Safety was similar across groups with fewer opioid-related adverse events observed in the HTX-011 group.

Conclusions HTX-011 demonstrated significant reduction in postoperative pain through 72 hours with significant reduction in opioid consumption and a significant increase in the proportion of opioid-free subjects compared with saline placebo and the most widely used local anesthetic, bupivacaine HCl.

Trial registration number NCT03295721.